Anti-TNF in PsA: Aim for Remission?

Most -- but not all -- reach minimal disease activity.

There was some good news to round out the year for clinicians managing patients with psoriatic arthritis: a majority of patients are able to reach -- and sustain -- a state of minimal disease activity (MDA) with anti-tumor necrosis factor (TNF) therapy, Canadian researchers reported.

Among 226 patients in a single-center cohort, 64% achieved MDA within a mean anti-TNF treatment time of 1.3 years, and the mean duration of MDA was 3.46 years, according to Dafna D. Gladman, MD, and colleagues from the University of Toronto.

MDA has been defined as a state in which patients meet at least five of these criteria: they have no more than one tender or swollen joint or tender entheseal point, the Psoriasis Activity and Severity Index (PASI) score is no higher than 1, the patient pain score is 15 or lower, the patient global disease activity score is 20 or lower, and the Health Assessment Questionnaire score is 0.5 or less.

Sustained MDA, persisting for a year or more, has been shown to limit radiographic damage over 3 years, which is important because an estimated 40% to 60% of patients with psoriatic arthritis have developed erosive disease, even early in the course of disease.

Anti-TNF therapy has been shown to control disease activity and limit progression, but currently available guidelines don't address whether patients should continue or stop their medications once MDA is reached.

To address this and other concerns such as prognostic factors, Gladman's group examined outcomes from patients enrolled in the University of Toronto psoriatic arthritis cohort between 2000 and 2012 who were eligible for anti-TNF therapy after failing on conventional therapies.

Patients were assessed clinically every 6 to 12 months, and radiographs were obtained every 2 years.

A total of 65% of the patients were male, and mean age at the time of diagnosis was 36. Mean duration of psoriatic arthritis was 13 years, but as is typical, the skin component of the disease had been present far longer, for an average of 21 years.

Mean baseline PASI score was 3.3, mean number of active joints was 10.6, and 10% to 15% had dactylitis, enthesitis, or tenosynovitis. Joint damage was present in 14%.

Mean C-reactive protein was 6.7 mg/L, and the erythrocyte sedimentation rate was abnormal in one-quarter of the patients.

Most had previously been treated with nonsteroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs.

Among the 146 patients who reached MDA, 17 were able to reduce the dose of their TNF inhibitor, and eight of these stopped treatment. Most of these patients also were not taking other disease-modifying drugs at the time of dose reduction or treatment withdrawal.

A total of 13 of the 17 were men, whose disease duration was almost 11 years. In eight of them, no disease flares occurred during an average follow-up of 3.18 years.

While 64% of patients in this cohort did reach MDA, 36% did not, "suggesting that the TNF-alpha pathway might not have a pivotal role in driving the inflammation in such patients, who might benefit from other treatments targeted at different inflammatory pathways," Gladman and colleagues wrote.

At baseline, 23 patients in the cohort were already in MDA and were excluded from the study analysis. However, the authors noted that 14 of them showed evidence of active joint inflammation even though they met the established MDA criteria.

"This may explain why some patients with MDA accrue radiographic damage that may be the consequence of ongoing residual disease activity," they suggested.

"It also suggests that MDA may not be the ideal target, and that we should strive for complete remission," they added.

However, a firm definition for remission in psoriatic arthritis has yet to be established.

Limitations of the study included its observational design and the possibility of confounding by indication.

"Despite these limitations, the major findings of this study are highly important and relevant to both clinicians and patients treated with these drugs," the researchers concluded.

Among other major stories in psoriatic arthritis in 2014 were the findings of efficacy for a number of medications, the effects of smoking on disease, and predicting cardiovascular risks.

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